Augmented Mitochondrial Transfer Involved in Astrocytic PSPH Attenuates Cognitive Dysfunction in db/db Mice

Area of Science:

• Neuroscience
• Metabolic Disorders
• Cell Biology

Background:

• Diabetes-associated cognitive dysfunction (DACD) is a significant cause of mortality in diabetic patients.
• Phosphoserine phosphatase (PSPH) is key in L-serine biosynthesis and insulin signaling.
• CD38 mediates mitochondrial transfer and is activated by the insulin pathway.

Purpose of the Study:

• To investigate if astrocytic PSPH improves DACD by promoting mitochondrial transfer to neurons.
• To elucidate the mechanism by which astrocytic PSPH influences DACD.

Main Methods:

• Overexpression of PSPH in astrocytes of db/db mice.
• Morris Water Maze (MWM) test for cognitive function assessment.
• In vivo and in vitro analysis of spine density.
• Investigation of the insulin signaling pathway and CD38 expression.

Main Results:

• Overexpression of astrocytic PSPH alleviated DACD in db/db mice.
• PSPH stimulation increased astrocyte-derived mitochondrial transfer into neurons.
• Astrocytic PSPH amplified CD38 expression via the insulin pathway, promoting mitochondrial transfer.
• Increased spine density was observed both in vivo and in vitro.

Conclusions:

• Astrocytic PSPH plays a crucial role in alleviating DACD.
• The mechanism involves PSPH-mediated insulin pathway activation, leading to CD38 upregulation and enhanced astrocytic mitochondrial transfer.
• Targeting astrocytic PSPH presents a promising therapeutic approach for DACD.